The present invention, in some embodiments thereof, relates to medicine and, more particularly, but not exclusively, to novel compositions which are useful in inducing blood coagulation and/or in reducing or blocking hemorrhaging, for example, internal hemorrhaging.
Hemorrhaging, or bleeding, is a term used to describe a condition in which blood escapes from the circulatory system. Bleeding can occur internally, where blood leaks from blood vessels inside the body, or externally, either through a natural opening such as the mouth, nose, ear, urethra, vagina or anus, or through a break in the skin. By “internal hemorrhaging” it is meant that a blood vessel inside the body is injured and leaks. Blood leakage from internal blood vessels can be manifested also as external hemorrhaging, yet the injured blood vessel, which is the source of hemorrhaging, is internal.
Coagulation, also known as clotting, is the process by which liquid blood forms a clot. Coagulation may result in hemostasis, a term known to describe the cessation of blood loss from a damaged vessel. The mechanism of coagulation, as is well-described in the art, involves both activation, adhesion, and aggregation of platelets and deposition and maturation of fibrin.
An anti-hemorrhagic agent is a substance that promotes hemostasis and arrests bleeding, and is also referred to in the art as a hemostatic agent, a hemostat, or as a pro-coagulant.
Currently used anti-hemorrhagic agents can be categorized into systemic drugs, which act by inhibiting fibrinolysis or promoting coagulation; and locally-acting hemostatic agents, which act by causing vasoconstriction or promoting platelet aggregation.
Anti-hemorrhagic, or hemostatic, agents are typically used during surgical procedures to achieve hemostasis. Locally-acting hemostatic agents, however, have been gaining popularity for use in emergency bleeding control, particularly for internal hemorrhaging caused by severe trauma.
Exemplary known hemostats include microfibrillar collagen hemostat (MCH), which is a topical agent composed of resorbable microfibrillar collagen, typically used in surgical procedures; Chitosan hemostats, which are also topical agents composed of chitosan and its salts, act by bonding with platelets and red blood cells to form a gel-like clot which seals a bleeding vessel, and are known to be used to stop traumatic life-threatening bleeding; zeolites, such as the product QuikClot, act as absorbents, and are used for sealing severe injuries quickly; Thrombin and fibrin glue products are used surgically to treat bleeding and to thrombose aneurysms; desmopressin is used to improve platelet function by activating arginine vasopressin receptor 1A; Tranexamic acid and aminocaproic acid inhibit fibrinolysis, and lead to a de facto reduced bleeding rate. Some foam-forming agents have also been developed, which, once applied, form a foam that physically reduces bleeding by applying pressure to the blood vessels. The formed foam should thereafter be surgically removed.
Internal hemorrhaging (or bleeding) due to blunt or penetrating, civilian or military, trauma is known to cause major loss of human life, as well as drainage of hospital and blood bank resources. Among the most lethal injuries are civilian and military injuries that cause internal hemorrhaging.
Common traumas that lead to internal hemorrhaging include injuries of solid abdominal organs such as liver, spleen, kidneys and other organs. These injuries are commonly treated by surgical techniques such as suturing, resection and devascularization of the organ. A large number of liver, spleen and renal injuries do not respond to these techniques, leading to death of the patient or sacrifice of a valuable organ.
Moreover, sever internal hemorrhaging can lead to rapid and heavy loss of blood and death prior to the availability of the surgical treatment.
Blocking internal hemorrhaging by techniques which can be applied within a short time upon the injury is therefore highly sought for, with the goal being agents or compositions which can arrest massive internal bleeding within several minutes from the injury and preserve the blockage for at least a few hours, for example, until a surgical treatment can be provided to the injured subject (e.g., until the subject is brought to a hospital).
Citrate salts are known anti-coagulation agents. Some compositions containing a citrate salt in combination with pH-adjusting agents such as sodium bicarbonate, or sodium carbonate, have been described, in which the sodium carbonate or bicarbonate are used to prolong the anti-coagulation activity of citrate by maintaining a non-acidic pH.
WO 2015/166497, by the present assignee, describes that calcium carbonate, for example, in the form of aragonite extracted from the skeleton of the corals acts as an anti-coagulation or de-coagulation agent.
U.S. Pat. No. 5,985,315 describes a device for isolation of blood coagulation components using coral skeleton made of calcium carbonate. Some of the blood fractions passed through the device are described therein as human blood anti-coagulated by citrate.